Treatment With Dinutuximab Beta, Zoledronic Acid and Low-dose Interleukin (IL-2) in Patients With Leiomyosarcoma

Prior treatment

• Patients after allogenic stem cell transplantation or other allogenic organ transplantation (e.g., liver, kidney etc.).
• Patients who have received prior anti-GD2 therapy, including chimeric antigen receptor (CAR) T cells directed against GD2 antigen.

Other illness

• Patients with a known history of hypersensitivity to interleukin-2.
• Patients with a hypersensitivity to zoledronic acid or to other bisphosphonates.
• Patients with different malignant diseases other than sarcoma (measurable manifestations in the last 12 months or active therapy against the other malignant disease in the last 12 months).
• Known active pulmonary disease with hypoxia defined as:
  • Oxygen saturation \< 85% on room air or
  • Oxygen saturation \< 88% despite supplemental oxygen.
• Uncontrolled intercurrent illness including, but not limited to, poorly controlled hypertension or diabetes, ongoing active infection, or psychiatric illness/social situation that may potentially impair the participant's compliance with study procedures.
• Any condition that, in the opinion of the investigator, would compromise the well-being of the participant or the study or prevent the participant from meeting or performing study requirements.

Other

• Symptomatic, untreated, or uncontrolled brain metastases present.
• Need for invasive dental procedures. Preventive dental exams should be performed before starting zoledronic acid.
• Lactating females are not eligible unless they have agreed not to breastfeed their infants.

• Patients must have histologically confirmed leiomyosarcoma.
• ≥ 1 prior systemic therapy for sarcoma, including adjuvant systemic therapy (anthracycline-containing regimen).
• Patients must have a cryopreserved and formalin-fixed paraffin-embedded tumor sample available for submission to central pathology review.
• Signed Written Informed Consent.
• Men and women aged ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Measurable disease.
• Locally advanced/unresectable or metastatic disease.
• No prior therapy with any agent targeting GD2.
• Confirmed GD2-Expression proven on cryopreserved tissue tumor samples. A staining score of 2 on cryopreserved tissue is sufficient for enrollment of the patient.
• No treatment with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, or radiation ≤ 21 days before study registration.
• No participation in another clinical trial in the period 30 days prior to start of first dose.
• Patients should have resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE, version 5.0, grade 1 or less.
• Not pregnant and not nursing; for women of childbearing potential who are sexually active, a negative pregnancy test (urinary or serum beta-HCG) done ≤ 7 days prior to treatment start is required.
• Absolute neutrophil count (ANC) ≥ 1,000/mm3.
• Platelet count ≥ 70,000/mm3.
• Creatinine ≤ 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \> 45 mL/min.
• Total bilirubin ≤ 1,5 x upper limit of normal (ULN). If total bilirubin is greater than 1,5 x ULN, measure indirect bilirubin to evaluate for Gilbert's syndrome (if direct bilirubin is within normal range, participant may be eligible).
• AST/ALT ≤ 2.5 x upper limit of normal (ULN).
• Adequate pulmonary function (FEV1 \> 2 liters or ≥ 75% of predicted for height and age).
• No clinical significant heart failure (NYHA\<III) or ejection fraction (echocardiography or scintigraphy; EF \> 40%)
• Female participants must be postmenopausal (no spontaneous menses for at least 2 years), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent (at the discretion of the investigator), or if sexually active, have agreed to use an highly effective contraceptive method for the duration of their study participation (see Appendix 3 for guidance); patients should maintain adequate contraception for a minimum of 2 months after the last dose of dinutuximab beta. Male participants must agree to use an adequate contraception method as deemed appropriate by the investigator (e.g., vasectomy, double-barrier, partner using effective contraception) and to not donate sperm for a minimum of 5 months after treatment discontinuation.